An electro-optical analysis system designed to optimize simultaneous or linked optical and electrical measurements and stimulation of transmembrane cell signals in living cells will be developed. The facility is based on fluorescence microscopy with low noise, image-enhanced video image detection, with digital image recording and analysis to achieve ultimate sensitivity and resolution for optical mapping of membrane potential, Ca++ and H+ gradients, and fluorescence labeled receptor distribution. Simultaneously, single channel electrical recording of membrane channels in situ and reconstituted into liposomes with responses at the picoSiemen conductance level is enabled by patch clamping electronics and coupled micromanipulators. Optical switching of photostimulated ligands and topographical mapping of responses coincident with local signals is enabled by a combination of patch clamping, micromanipulation, optical detection and digital analysis, and stimulation light sources in one setup. Associated facilities include laser Raman microspectroscopy and standard fluorescence microscopy.